Abstract

Scaffold-seeded macrophage transplantation to a skin wound site accelerates healing.

The next time you get a paper cut or burn your hand while cooking, pay attention to how quickly it heals. The ability to heal rapidly becomes impaired with aging and onset of disease processes, such as diabetes. Although many studies have focused on the local cells responsible for wound healing, inflammatory cells also play a central role. A recent impressive study by Hu and colleagues demonstrates the role of monocytes and macrophage subpopulations in normal and pathologic skin wound healing. It is known that diabetic patients have impaired wound healing, however using autogenous macrophages to stimulate wound healing under diabetic conditions has not been previously described.

Hu et al. used a novel hydrogel delivery system to transplant nonpolarized macrophages in a mouse wound healing model and then elegantly characterized how these transplanted macrophages differentiated into different subpopulations using microfluidic technology. Mice were subjected to a humanized wound healing model where a full thickness skin wound injury was splinted open to allow for epithelialization rather than contraction. Wounds were then treated with a hydrogel scaffold seeded with a supraphysiologic number of macrophages. Wounds with transplanted macrophages on their hydrogel healed more rapidly than scaffold alone controls, seen as early as four days after injury and persisting until complete wound healing. Next, using single-cell analysis of the macrophages from their in vivo model, they showed that the macrophages differentiated into a mixed inflammatory (M1) and reparative (M2) phenotype and that transplanted macrophages express inflammatory cytokines. To translate this to a system of pathologic wound healing, they next transplanted macrophages from diabetic mice into a diabetic wound. Surprisingly, macrophages from diabetic donors accelerated diabetic wound healing and survived through complete healing. Last, they showed that human monocyte transplantation from healthy and diabetic donors accelerated wound healing in immunocompromised mice.

This study further defines the important role of macrophages in both normal and pathologic skin wound healing. Additional studies are needed to determine if the therapeutic use of macrophages can be further enhanced by skewing or enriching macrophages to a more reparative subpopulation. The positive role of macrophages in wound healing may give clinicians a cell-based therapy for the millions of wounds seen annually worldwide. Additionally, harnessing the cytokines secreted by the macrophages also holds promise for future translational efforts.